Phosphodiesterases (PDEs) are a family of enzymes encoded by 21 genes and subdivided into 11 distinct families according to structural and functional properties. These enzymes metabolically inactivate widely occurring intracellular second messengers, 3′,5′-cyclic adenosine monophosphate (cAMP) and 3′,5′-cyclic guanosine monophosphate (cGMP). These two messengers regulate a wide variety of biological processes, including pro-inflammatory mediator production and action, ion channel function, muscle contraction, learning, differentiation, apoptosis, lipogenesis, glycogenolysis, and gluconeogenesis. They do this by activation of protein kinase A (PKA) and protein kinase G (PKG), which in turn phosphorylate a wide variety of substrates including transcription factors and ion channels that regulate innumerable physiological responses. In neurons, this includes the activation of cAMP and cGMP-dependent kinases and subsequent phosphorylation of proteins involved in acute regulation of synaptic transmission as well as in neuronal differentiation and survival. Intracellular concentrations of cAMP and cGMP are strictly regulated by the rate of biosynthesis by cyclases and by the rate of degradation by PDEs. PDEs are hydrolases that inactivate cAMP and cGMP by catalytic hydrolysis of the 3′-ester bond, forming the inactive 5′-monophosphate (Scheme 1).

On the basis of substrate specificity, the PDE families can be divided into three groups: i) the cAMP-specific PDEs, which include PDE4, -7 and -8; ii) the cGMP-selective enzymes PDE5 and -9; and iii) the dual-substrate PDEs, PDE1, -2 and -3, as well as PDE10 and -11. The discovery of phosphodiesterase 10A (PDE10A) was reported in 1999. Of all the 11 known PDE families, PDE10A has most restricted distribution with high expression only in the brain and testes. In the brain, PDE10A mRNA and protein are highly expressed in the striatum. This unique distribution of PDE10A in the brain, together with its increased pharmacological characterization, points to the potential use of PDE10A inhibitors for treating neurological and psychiatric disorders like schizophrenia.
Positron Emission Tomography (PET) is a non-invasive imaging technique that offers the highest spatial and temporal resolution of all nuclear imaging techniques and has the added advantage that it can allow for true quantification of tracer concentrations in tissues. It uses positron emitting radionuclides such as, for example, 15O, 13N, 11C and 18F for detection.
WO-2006/072828 (Pfizer) discloses heteroaromatic quinoline compounds as selective PDE10 inhibitors. WO-2007/129183 (Pfizer) discloses bicyclic heteroaryl compounds as PDE10 inhibitors.
Zhude Tu et al. disclose [11C]-papaverine as a PET tracer for imaging PDE10A (Nuclear Medicine and Biology, 37, 509-516, 2010) and conclude that it is not an ideal radioligand for clinical imaging of PDE10A in the central nervous system. It is opined that analogues are required having higher selectivity for PDE10A over PDE3 and improved pharmacokinetic properties.
WO-2010/097367 discloses radiolabelled quinoline compounds, e.g. -2-{4-[1-(2-[18F]fluoroethyl)-4-pyridin-4-yl-1H-pyrazol-3-yl]-phenoxymethyl}-quinoline, useful as PDE10A ligands.